Nucleic acids have generated great interest for use in treating diseases, such as cancer. In spite of their potential in cancer therapy, nucleic acids such as small interfering RNAs (siRNAs) and micro RNAs (miRNAs) can have limitations. First, these nucleic acids can be vulnerable to degradation by enzymes that are ubiquitous in the environment. Second, the effects of nucleic acids (such as siRNAs and miRNAs) are typically transient. Third, nucleic acids themselves cannot enter the cells and the existing delivery systems are either of low delivery efficiency or fail to prolong circulation in the body after systemic administration.
Photodynamic therapy (PDT) can also be an effective anticancer treatment option. PDT involves the administration of a tumor-localizing photosensitizer (PS) followed by light activation to generate highly cytotoxic reactive oxygen species (ROS), particularly single oxygen (1O2), which trigger cell apoptosis and necrosis. By localizing both the PS and the light exposure to tumor regions, PDT can selectively kill tumor cells while preserving local tissues. PDT has been used to treat patients with many different types of cancer, including head and neck tumors, breast cancer, gynecological tumors, brain tumors, colorectal cancer, mesothelioma, and pancreatic cancer. The use of PDT for treating cancers in the head and neck is particularly advantageous over traditional treatment modalities, e.g., surgery and irradiation, as PDT causes less destruction of surrounding tissues and reduces aesthetic and functional impairments. Porphyrin molecules such as PHOTOFRIN®, VERTEPORFIN®, FOSCAN®, PHOTOCHLOR®, and TALAPORFIN® are among the most commonly used PSs for PDT. However, although they have efficient photochemistry for ROS generation, their suboptimal tumor accumulation after systemic administration can limit the efficacy of PDT in the clinic.
Accordingly, there is an ongoing need for additional delivery vehicles for improving the delivery (e.g., the targeted delivery) of both nucleic acid and PS therapeutics. In particular, there is a need for delivery vehicles that can deliver nucleic acids or PSs in combination with other therapeutics (e.g., non-nucleic acid/non-PS chemotherapeutics) in order to increase treatment efficacy, e.g., by overcoming drug resistance by treating cancers via multiple mechanisms of action.